Central Pain Syndrome (CPS) is characterized by severe and excruciating pain resulting from a lesion or pathology in the spinal cord, brainstem, or thalamus, and is highly resistant to any therapy or medication. Its cause is unknown. My objective is to develop a rodent model of CPS with which we can begin to understand the cellular mechanisms underlying this debilitating condition and test potentially useful therapeutic targets for its treatment and/or prevention. I hypothesize that a lesion of ascending sensory input pathways in the spinal cord of rats or humans causes partial denervation of relay cells in the ventrobasal complex of the thalamus resulting in a delayed increase in their excitability. This hyperexcitability might result from either increased intrinsic neuronal excitability (e.g. a downregulation of K+ channels or upregulation of Ca2+ channels) and/or increased network excitability (e.g. altered synaptic inhibition or excitation). The hypothesis predicts that drugs that display anticonvulsant activity in absence epilepsy, such as ethosuximde, will reduce excessive thalamic excitability and relieve central pain syndrome. I will test these hypotheses by investigating the perception of pain with well established behavioral paradigms, and the intrinsic and network excitability of thalamic neurons in ex vivo brain slices from rats in which ascending nociceptive pathways in the spinal cord have been lesioned. In addition, I will test whether ethosuximde and other 'thalamic' antiepileptic drugs effectively restore normal pain perception and decrease the excitability of thalamic neurons in brain slices from injured rats. These experiments should increase our understanding of the genesis of this devastating condition and point the way to sorely needed therapeutic relief. I will attempt to develop a model of Central Pain Syndrome, a form of excruciating pain suffered by victims of head or spinal injuries, in rats so that we can understand the biological causes of this debilitating condition and suggest new ideas for treating or preventing it. [unreadable] [unreadable] [unreadable] [unreadable]